Compositions and methods for hair regrowth

ABSTRACT

The disclosure provides compositions and methods for promoting hair growth and reducing hair loss using bioactive extracts of curcumin, Withania somnifera, and saw palmetto. Tocotrienols, tocopherols, piperine extract, low molecular weight collagen, and hyaluronic acid are optionally included in the compositions and methods

Throughout this application various publications are referenced. Thedisclosures of these publications in their entireties are herebyincorporated by reference into this application in order to more fullydescribe the state of the art to which this invention pertains.

FIELD OF THE INVENTION

The present disclosure relates to the field of hair loss, and moreparticularly to the restoration of hair growth.

BACKGROUND OF THE INVENTION

Hair loss (alopecia) is a widespread problem affecting about 80 millionmen and women in the United States alone according to the AmericanAcademy of Dermatology. The $7 billion hair loss industry is a testamentto the significance and the scope of the issue. The most commonalopecias are androgenic alopecia, telogen effluvium and alopeciaareata.

Androgenic alopecia (AGA) is the most common type of hair loss in bothsexes, affecting at least 50% of men by the age of 50 and up to 40% ofwomen in mid-adult life. More recently AGA is being referred to as malepattern hair loss (MPHL) and female pattern hair loss (FPHL) to reflectthe differences in clinical presentation and the new science on thepathophysiology of the conditions, which support the modernunderstanding that hair loss is due to the contribution of otherfactors, besides androgens and genetic disposition, particularly inFPHL.

In humans, individual hair follicles progress through phases of growthindependent of one another. They are subject to and respond individuallyto the influence of several inductive and inhibitory signaling moleculesin the follicle environment. Anagen, the growth phase, generally lastsbetween 2 to 7 years in a healthy follicle. Catagen is a transitionalphase of regression that lasts approximately 2-3 weeks between thegrowth phase and the resting phase. Telogen, the resting phase, lastsfor approximately 3 months. The late stage of telogen is associated withthe regeneration of the next growth phase. Loss of coverage, or hairthinning and hair loss, occurs when the normal cycling and growth ofnumerous follicles are disrupted. The disruption can be widespread,sudden and synchronized causing immediately visible loss or it can beslow, steady and unsynchronized, becoming visible over a long period oftime, only when 50% of the follicles have been affected. Hair densityand volume decreases when the hair growth cycle is disrupted and morefollicles enter catagen and telogen prematurely, while not enoughfollicles enter anagen to replace them. Further, miniaturization, thesignature pathology seen in patients with MPHL & FPHL, can occur wherethe width of hair fibers progressively decrease in each consecutivecycle causing once thick and long hair fibers to become thinner,lighter, barely visible vellus-like hairs.

A modern view on alopecia describes all hair loss, regardless of itsvarious manifestations and traditional classifications, as the result ofa ‘disordered hair follicle.’ (Breitkopf, T., Dermatol. Clin., 2013,31(1):1-19). When hair follicles on the scalp are in an unbalanceddisordered state, it compromises their function and manifests in hairgrowth and cycle abnormalities. Different combinations of abnormalitiespertain to different disorders. The traditional view held by researchersand clinicians considers hair loss as a disease, which has led toalopecias being classified by their presumed respective causes and/ormanifestations. For instance, MPHL/FPHL and telogen effluvium (TE) areclassified as non-inflammatory, whereas alopecia areata (AA) andscarring alopecias are classified as inflammatory diseases. Recentfindings have begun to challenge this perspective as researchers havefound that even in MPHL/FPHL there is significant evidence ofmicro-inflammation, a term proposed to reflect the indolent inflammatoryprocess in AGA. (Mahe, Y. F., Int. J. Dermatol., 2000, 38(8):576-84).Thus, it is being recognized that in all alopecias there are multiplecombinations of factors, like inflammation, that underlie the disorderedhair follicle.

The hair growth cycle is primarily maintained through the complexinterplay of numerous cytokines, growth factors and transcriptionfactors that signal the cells of the follicles to either induce orprohibit hair growth. These signals are both introduced extrinsicallyand also produced intrinsically by the follicle's dermal papilla cells(DPCs) that determine follicle and hair fiber characteristics. Thoseextrinsic controls that induce early catagen and inhibit growth, such asthe androgen dihydroxytestosterone (DHT), have provided targets fortherapies, such as the drug finasteride in the case of DHT. However,even extrinsic factors act on the follicles by altering the productionof signaling molecules by the follicle DPCs. The significance of immunesignaling and balance in sustaining proper follicle functioning isfurther underscored by the fact that it represents one of the few sitesof ‘immune privilege’ (IP) in the body. The follicle's IP normallyprotects the follicle from immune system recognition and inflammatoryattack. IP also works to sequester anagen-associated autoantigens withinthe follicle, protecting them from immune recognition. Studies haveshown that the follicle's IP can be compromised by stress-inducedneuropeptides such as Substance P (SP) (Peters, E. M., Am. J. Pathol.,2007, 171(6):1872-86) and cytokines such as interferon gamma (IFN-γ).(Xing, L., Nat. Med., 2014, 20(9):1043-49). Subsequent to this immunesystem imbalance and collapsed IP, compromised follicles are subject toinflammatory attack. Thus, for a follicle to not become ‘disordered’ andto produce healthy hair, it is vital to maintain an IP.

Inflammatory responses can be further stimulated by the presence of freeradicals, also referred to as Reactive Oxygen Species (ROS). ROS arehighly reactive molecules with unpaired electrons that can directlydamage cellular structures and alter DNA. They are generatedendogenously through normal and specific metabolic processes and we aresubject to ROS exposure from the environment, for instance in the formof common air pollutants. However, with age, the body's ability toneutralize ROS decreases since production of antioxidant enzymes andendogenous antioxidants decreases with age while ROS generationincreases with age resulting in increased oxidative stress on the body,including hair. Compromised hair follicles are known to be particularlyvulnerable to ROS from environmental stressors. Further, inflammatoryresponses, through positive feedback, create a cyclic cascade andgenerate even more ROS. For example, it has been shown in androgeninduced alopecia that the generation of ROS mediates thepro-inflammatory androgen signaling cascade. Similarly, in models ofchronic stress, the neurogenic inflammatory pathways of SP were shown toincrease ROS and decrease innate antioxidant defenses, leading to hairgrowth arrest and hair cycle arrest.

Thus, the common underlying pathway of hair loss can be seen asdisordered immune signaling and an oxidative imbalance that involvenumerous players: pro-inflammatory cytokines, pro-fibrotic and growthinhibiting factors like TGF-β, and inflammatory cells—all perpetuatedthrough chronic generation of free radicals, oxidative stress andfurther inflammatory changes and immune imbalances. This common pathwayin hair loss can be triggered and propagated by several factorsincluding, but not limited to: sudden changes or severe imbalances innutrition as in crash diets, androgens, genetics, and stress.

Androgens, like other steroid hormones, act on target cells by diffusingthrough the plasma membrane, binding to specific receptors and thenacting on the DNA, inducing the transcription and translation ofspecific hormone-regulated genes and their products, such as cytokines.In the follicle, testosterone is mostly metabolized by 5α-reductase(5-ar) into DHT. DHT is implicated in the pathogenesis of severalandrogen responsive disorders such as prostate disease, acne and AGA. Itis now recognized that the effects of androgens within follicles aremediated via signaling cascades, which are dysregulated in pathologieslike hair loss. The main action of DHT on follicles occurs within thedermal papilla cells, where it binds to androgen receptors, enters thenucleus and leads to increased transcription and overproduction ofgrowth-inhibiting molecules like the cytokine TGF-β that signals catageninduction and apoptosis. Once triggered by minimal amounts of DHT, otherfactors can maintain the pathophysiology of AGA without the presence ofandrogens, as seen in men with MPHL who were castrated after puberty.Thus, it appears that blocking androgens alone to combat hair loss isinsufficient due to the presence of signaling and dysregulation of theimmune balance downstream of the initial insult, triggering a cascade ofnumerous immune and inflammatory processes that can sustain the alopecicpathway. In fact, androgen-induced overproduction of TGF-β by the DPC'sand surrounding fibroblasts also plays a role in perifollicular fibrosisand inflammation—implicated in the pathophysiology of miniaturization infollicles. Of special note, MPHL and FPHL differ in that women have lesstotal 5-ar than men. This may account for why current drug therapiesthat block 5-ar to treat alopecia produce minimal results in women ascompared to men, especially given that systemic DHT and 5-ar aregenerally within normal limits in women with FPHL.

Stress has long been disputed as playing a measurable role in hair loss.Recent research, however, has begun to examine the roles ofpsycho-emotional stress, nerves and immune cells in hair growth and hasdiscovered new pathways that link the central nervous system with thehair follicle. New evidence provides definable neurological,neuroendocrine and immunological mechanisms through which stress caninhibit hair growth. Psycho-emotional stress results in systemicelevation of nerve growth factor, a key modulator of hair growthtermination, and substance P (SP), the prototypic stress-associatedneuropeptide that is widely acknowledged as a potent modulator of immuneresponses and neurogenic inflammation of the skin. In addition tocompromising follicle IP, elevated levels of SP induce the proliferationand degranulation of local mast cells and these mast cells in turnrelease a host of pro-inflammatory mediators like histamine andcytokines like TNF-α. The resulting neurogenic inflammation has beenshown to cause hair growth arrest and promotion of follicle regression.The follicle has also been shown to be highly sensitive to stresshormones like cortisol, which are known to cause catagen induction, andthe follicle even contains all the needed machinery to self-producethese hormones. Specifically, one of the major stress hormones,corticotropin-releasing hormone (CRH), is elevated systemically duringstress and can bind to the follicle, which induces the follicle toproduce even more CRH and cortisol.

There are limited options regarding pharmaceutical therapeutics for thetreatment of AGA in the United States, and only one is indicated forFPHL. One therapeutic, is minoxidil. While minoxidil's mechanism ofaction has not been clarified despite its use since 1988 in thetreatment of AGA, it is widely believed to elongate the anagen phase byacting on potassium channels in the hair follicle, thereby improvingfollicular circulation. Some known side effects of minoxidil aredizziness, chest pain, difficulty breathing and swelling. The topicalversion has the further side effects of causing rashes and skinirritations in some users. The other FDA-approved therapeutic,finasteride, is only indicated in MPHL. It works by competitivelybinding the enzyme 5-ar, thereby reducing the conversion of testosteroneinto DHT, which is a known androgen trigger for hair loss. Finasterideis FDA-approved for treatment of AGA only in men and has also beenreported to cause side effects of erectile dysfunction, ejaculatorydysfunction and loss of libido in a segment of users.

The complexity of the hair loss pathway requires a multi-prongedapproach to treat the most prominent aspects of the problem.Pharmaceutical therapies such as minoxidil and finasteride achieve somesuccess in treating hair loss, but ultimately only address singleelements of a larger problem, not addressing downstream dysregulatedsignaling or the common pathway of inflammation and oxidative stress.Additionally, they are associated with potential significant anddebilitating side effects. There is a need for a therapy which inaddition to addressing just one trigger, like androgens, also addressesthe disordered immune signaling of catagen-inducing cytokines andaddresses the inflammation that is both a result and a promoter of thedisordered signaling. An ideal therapeutic should further address thegeneration and effect of ROS in hair loss due to the role of oxidativestress in aggravating inflammation. And, importantly, there is a needfor a therapy which can also address psycho-emotional stress and itseffects on hair loss. Finally, there is a need for a therapy that issafe and does not induce similar side effects.

Nutraceutical formulations and the multi-targeting bioactive propertiesof certain plant phytonutrients offer a possible solution since they cantarget multiple triggers of hair loss at once. Further, the fact thatthese phytonutrients are natural in origin and known to be safe forconsumption avoids many of the concerns of undesired side effects, whichare common with pharmaceuticals.

One such phytonutrient is curcumin (diferuloyl methane) which is foundin the rhizome of the turmeric plant, Curcuma longa, and is readilyextracted from the plant, U.S. Pat. No. 5,861,415. Curcumin has beenshown to slow hair loss by down-regulating expression of the DHT-bindingAndrogen Receptor, inhibit type II 5-ar, support regrowth by decreasinglevels of the catagen-signaling cytokine TGF-β and to be a potentantioxidant and anti-inflammatory agent. (Pumthong, G., J. Dermatolog.Treat., 2012, 23(5):385-92). It has significant activity againstpro-inflammatory cytokines like TNF-α and IL-1, both known to signalcatagen and to inhibit follicle growth. Curcumin's anti-stress andneuroprotective properties have been studied extensively and oneneurotransmitter it inhibits is Substance P, which in high levels hasbeen shown to compromise the follicle's immune privilege and to inducemast cell degranulation that leads to catagen, hair growth inhibitionand increased inflammation. As for its safety profile, curcumin has notbeen shown to evidence toxicity in human studies at doses of up to 8000mg daily for three months. (Cheng, A. L., Anticancer. Res., 2001,21(4B):2895-2900).

Another phytonutrient is Withania somnifera, commonly known asAshwagandha. It is a medicinal plant that has been employed forcenturies in ayurvedic medicine and has recently been observed to reducehair loss. (Kalani, A., BMJ Case Rep., 2012). Ashwagandha has also beenrecognized as an adaptogen, a unique class of herbal ingredients thatresult in the restoration of normal physiological function(homeostasis), and to increase the body's resistance to the effects ofstress, such as by decreasing cellular sensitivity to stress.Ashwagandha is known to rebalance and lower the levels of the stresshormone cortisol, to improve thyroid function, and to elevate the body'sendogenous antioxidant enzymes through its principal withanolides.Ashwagandha also exhibits inhibitory effects on pro-inflammatorycytokines such as IL-6 and TNF-α. The active compounds in Withaniasomnifera leaves and roots are C28 steroidal lactone molecules known aswithanolides, such as Withaferin A, and are extracted from the plantusing known methods, U.S. Pat. No. 7,108,870.

Extracts of Serenoa repens or “saw palmetto,” a dwarf palm tree, havebeen observed to help hair regrowth in male pattern baldness. (Chittur,S., Evid. Based Complement Alternat. Med., 2011:985345). The sawpalmetto berry contains over 100 known compounds. The active ingredientsin saw palmetto are contained in the purified lipid soluble extract ofthe saw palmetto berry. This has been found to contain 85 to 95 percentfatty acids (predominantly lauric, caprylic, and caproic), long chainalcohols, and sterols (including beta-sitosterol, stigmasterol,cycloartenol, lupeol, lupenone, and methylcycloartenol). Saw palmettonaturally inhibits the activity of the testosterone catalyzing 5-arenzyme, but unlike the drug finasteride it does not interfere withProstate Specific Antigen levels. In comparative studies withfinasteride, saw palmetto was even associated with an improvement ofsexual dysfunction. (Suter, A., Phytother. Res., 2013, 27(2):218-26).The berries also contain high molecular weight polysaccharides (sugars),which may reduce inflammation or strengthen the immune system.

Tocotrienols, together with tocopherols, which are members of theVitamin E family, possess potent antioxidant activity by directlyneutralizing reactive oxygen species and also raising the body's ownantioxidants and antioxidant enzymes. Tocotrienols have also been shownto provide protection against UV light and oxidative stress and topromote hair regrowth in humans. (Beoy, L. A., Trop. Life Sci. Res.,2010, 21(2):91-99). A natural source rich in tocotrienols andtocopherols is palm oil, with crude palm oil (also referred to as the“tocotrienol-rich fraction”) containing up to 800 mg/kg weight of α- andγ-tocotrienol isotypes. The distribution of vitamin E in palm oil is 30%tocopherols and 70% tocotrienols. Natural sources of vitamin E, such aspalm oil, are believed to have greater bioactivity than syntheticallymanufactured vitamin E.

Piperine, the active principle of the dried, unripe fruits of variousblack pepper plants, is an alkaloid which has been shown in in vitrostudies to protect against oxidative damage by inhibiting or quenchingfree radicals and reactive oxygen species. It has also been shown toenhance the bioavailability of a number of therapeutic drugs andphytonutrients like curcumin by strongly inhibiting hepatic andintestinal aryl hydrocarbon hydroxylase and UDP-glucuronyl transferase.(Srinivasan, K., Crit. Rev. Food Sci. Nutri., 2007, 47(8):735-48). Inaddition to possessing antioxidant properties, piperine has further beenshown to possess analgesic and anti-inflammatory properties in animalstudies. (Tasleem, F., Asian Pac. J. Trop. Med., 2014, 7S1:S461-8).

Healthy thyroid function is crucial to the metabolism of almost alltissues, hair follicles included. The metabolic effects of the thyroidcome from two iodine containing-hormones, triiodothyronine (T3) andthyroxine (T4). Hair follicles (HFs) are very sensitive to thyroidhormones (Stenn K S., Physiol Rev. 2001 81:449-94.). Research has shownthat human scalp hair follicles are direct targets for TSH thyroidstimulating hormone (TSH) which has various functions that benefit hairgrowth (Bodo E., Journal of Investigative Dermatology. 2009 129:1126-1139). TSH also directly upregulates the “master antioxidant”glutathione peroxidase and mitochondrial transcription factors in humandermal papillae fibroblasts further supporting a role for TSH signalingin HF metabolism and oxidation processes (Id). Thyroid hormones alsoinduce substantial modifications in mitochondrial inner membrane proteinand lipid compositions that are involved in mitochondrial biogenesis.(Harper, M E., Thyroid. 2008; 18(2):145-56). It has been reported thatinhibition of mitochondrial protein synthesis can increase an area ofhair loss by 30-80% (Hyde, G E., Otolaryngology—Head and Neck Surgery.1995; 113:530-540).

The hair follicle also has a high affinity for environmental pollutantssuch as toxins and some of these toxic chemicals are stored in thekeratinized structures at the hair follicle (Pierard, G E., Journal ofCutaneous Pathology, 1979:6: 237-24). Hair loss patterns, such asdiffuse alopecia, are directly related to ingestion, subjection, andaccumulation of toxic metals from the environment. Mercury is an exampleof one such heavy metal that can cause hair loss by accumulating in thethyroid and subsequently reducing iodide uptake at the sodium/iodidesymporter by binding to iodide; decreasing the rate of synthesis ofthyroid hormones (Chen, A., Environ Health Perspect., 2013 February;121(2): 181-186).

In addition to being a necessary factor in healthy thyroid function,iodine is known as one of the best natural chelators in our body as itbinds to toxic metals to form complex structures which are easilyexcreted from the body (H SGK., Marcel Dekker Inc. 1988). As an example,iodine has the ability to increase mobilization of bromine from storagesites resulting in increased urinary excretion of bromide (Sircus, D M.,Lulu Press; 2016). By chelating toxins from the body, iodine allowsminerals that are essential to our hair health, such as selenium, tosupport the hair growth cycle. Iodine is a component of kelp, and of allspecies of kelp it is found in the highest concentration in the speciesLaminara digtata.

Iodine is one component of kelp, and of all species of kelp it is foundin the highest concentration in the species Laminara digtata. Kelpincludes several other vitamins and minerals necessary for an optimalhair growth cycle. One of these minerals is choline. It was found thatthe addition of choline to a bioavailable form of silica improved thetensile strength (elasticity and break load) of hair and resulted inthicker hair (Wickett R R., Arch Dermatol Res. 2007 December;299(10):499-505). Calcium is another component of kelp that hasbeneficial effects for hair. Calcium has the ability to not onlyinteract with signal pathways that are essential to hair growth but toalso activate hair follicle stem cells that are in rest, quiescence, inorder for growth to occur (Yucel, G., Genes Dev. 2013: 27(11). 1217-22).Copper can also be found in kelp. Copper plays a role in thedifferentiation and proliferation of dermal papilla cells, which arespecialized fibroblasts that play an important role in the developmentof hair follicles (Kil M., Ann Dermatol. 2013: 25(4) 405-409).

It is an object of the present disclosure to provide a nutraceuticalsupplement composition that simultaneously inhibits the moleculartriggers of hair loss associated with stress and androgens and furtheraddresses the concurrent cascade of disordered cytokine signaling,inflammation and oxidative damage that is brought on by their activity,thereby preventing damage and shrinkage to hair follicles and promotingmore follicles to enter a healthy hair cycle in a multi-targeted,comprehensive manner.

Citation of any reference in this section of the present disclosure isnot to be construed as an admission that such reference is prior art tothe present disclosure.

SUMMARY OF THE INVENTION

Accordingly, the present disclosure provides a composition for promotinghair growth and reducing hair loss, comprising from about 100 to about1000 mg of an extract of Curcuma longa, from about 100 mg to about 1000mg of an extract of the roots and leaves of Withania somnifera, and atleast about 200 mg of saw palmetto extract. Advantageously, thecomposition further comprises from about 100 mg to about 1000 mg oftocotrienols and tocopherols. The composition may further comprise fromabout 225 mcg to about 300 mcg of iodine. The composition may furthercomprise low molecular weight collagen and hyaluronic acid and thecollagen may be Type I and Type III collagen and have a molecular weightof less than about 5000 daltons. The collagen may be present in anamount from about 500 mg to about 2000 mg, and said hyaluronic acid maybe present in an amount from about 100 mg to about 1000 mg.

The composition of the disclosure may further include at least about 200mg of curcumin, at least about 100 mg of withanolides, at least about200 mg of saw palmetto extract, at least about 225 mcg of iodine, and atleast about 100 mg of tocotrienols and tocopherols comprising a complexof about 78% tocotrienols and about 22% tocopherols, at least about 1000mg of Type I and III collagen having a molecular weight of less thanabout 3000 Daltons, and at least about 100 mg of hyaluronic acid.

The composition of the disclosure may further include at least about 5mg of piperine.

The composition of the disclosure may further include one or morecompounds from the group consisting of green tea extract, L-methionine,L-cysteine hydrochloride, resveratrol, capsaicin, biotin, selenium,Vitamin D, Vitamin A, and Vitamin C.

The disclosure provides a food item comprising a composition asdescribed herein, and a mixture of additional components selected fromthe group consisting of vitamins, amino acids, minerals, proteins,carbohydrates, fats, flours, flavoring, and sweetener.

The disclosure also provides a method of promoting hair growth andreducing hair loss by administering to a subject an effective amount ofa composition as described herein, in a pharmaceutically suitablevehicle, for a time sufficient to promote hair regrowth and reduce hairloss in subjects exhibiting symptoms of alopecia.

Additional features, advantages, and aspects of the present disclosureare set forth or apparent from consideration of the following detaileddescription, drawings, and claims. Moreover, it is to be understood thatboth the foregoing summary of the present disclosure and the followingdetailed description are exemplary and intended to provide furtherexplanation without limiting the scope of the present disclosure asclaimed.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are included to provide a furtherunderstanding of the present disclosure, are incorporated in andconstitute a part of this specification, illustrate aspects of thepresent disclosure and, together with the detailed description, serve toexplain the principles of the present disclosure. In the drawings:

FIG. 1 depicts the androgen pathway and indicates where components ofthe disclosure help mitigate damage to hair follicles.

FIG. 2 depicts how the stress pathway may lead to hair loss andindicates where components of the disclosure help mitigate damage tohair follicles.

FIG. 3 is a table depicting the subject's results of variousimplementations of the disclosure over a 7-month period.

FIG. 4 shows the results of the BrdU Proliferation Assay after 72 hoursof treatment with: Ashwaghanda alone, Kelp alone, Saw Palmetto alone,and combinations of Kelp and Saw Palmetto, Ashwaghanda and Kelp,Ashwaghanda and Saw Palmetto, and Kelp, Ashwaghanda and Saw Palmetto,solubilized respectively in 0.8% DMSO.

FIG. 5A-FIG. 5D show the results of a safety and efficacy evaluation ofa composition of the disclosure in promoting hair growth in women withself-perceived thinning hair. FIG. 5A shows the terminal hair count atbaseline, 3 months and 6 months in the active group vs. placebo. FIG. 5Bshows the vellus hair count at baseline, 3 months and 6 months in theactive group vs. placebo. FIG. 5C shows hair growth global improvementby investigator grading at 3 months and 6 months in the active group vs.placebo. FIG. 5D shows hair quality global improvement at 3 months and 6months in the active group vs. placebo.

FIG. 6A-FIG. 6F show images of an active subject at baseline (FIGS. 6Aand B), 3 months (FIGS. 6C and D) and 6 months (FIGS. 6E and F).

DETAILED DESCRIPTION OF THE INVENTION

The present disclosure provides novel nutraceutical compositions whichhave been shown to reduce hair loss and promote the growth of new hairin individuals suffering from various types and degrees of hair loss.Current treatments for hair loss and promotion of hair growth fall undertwo categories: a) pharmacological or b) nutrient supplements.Pharmacological treatments come with the risk of significant sideeffects and nutrient supplements only provide nutrition while ignoringthe ongoing causes of the actual hair loss itself. A non-pharmacologicalnutraceutical formulation, such as the compositions described herein,provides a much needed option for those who suffer hair loss, since itboth addresses the underlying causes of hair loss using natural remedieswithout pharmacological side effects and provides the nutrition neededfor improved hair growth. It can further be used as both a preventativeand as a complementary therapy to augment pharmacological treatments.

The present disclosure provides compositions and methods for promotinghair health and hair growth. Without being bound by any particulartheory or explanation, the novel nutraceutical compositions of thedisclosure contain components which may synergistically inhibit multipletriggers of hair loss such as DHT (see FIG. 1) and the stress hormonecortisol (see FIG. 2); reduce inflammation and oxidative stressassociated with the self-sustaining common pathway of hair loss; andprovide necessary nutrition which may be better absorbed and utilized byhair follicles after the follicles are rebalanced by the othercomponents of the compositions of the disclosure.

In one implementation of the disclosure for promoting hair growth andreducing hair loss, the composition comprises curcumin, ashwagandha, andsaw palmetto.

In another implementation of the disclosure for promoting hair growthand reducing hair loss, the composition comprises curcumin, ashwagandha,saw palmetto and iodine.

In a preferred embodiment for male subjects, the composition includes atleast about 200 mg of curcumin, at least about 100 mg of withanolides,and at least about 500 mg of bioactive saw palmetto, preferablystandardized to contain at least about 85% fatty acids and sterols.

In another preferred embodiment for hair regrowth and to reduce hairloss in female subjects, the composition of the disclosure furtherincludes at least about 200 mg of bioactive saw palmetto extract,preferably standardized to contain at least about 85% fatty acids andsterols. This embodiment containing less saw palmetto is preferred inwomen due to the fact that women typically have about 5 times less totaltestosterone than men. The same benefits can be achieved with less ofthis DHT inhibitor since women have less testosterone which can bemetabolized into DHT.

In a more preferred embodiment of the aforementioned compositions, thecompositions can additionally contain one or more of an effective amountof an extract from saw palmetto, tocotrienols, tocopherols, iodine,piperine, low molecular weight collagen, and hyaluronic acid.

The saw palmetto extract is preferably a bioactive extract of theSerenoa repens plant. Methods for obtaining the bioactive components ofthe disclosure are known, for example, by extraction of plant materials,as described in U.S. Pat. No. 6,039,950. The components can further beobtained with increased bioactivity and/or bioavailability, using knownmethods for improving the bioavailability of bioactive componentsextracted from plants, resulting in the need for less of the bioactivecomponent as described in U.S. Pat. Nos. 8,329,233, 6,153,198, and5,891,465. The bioactive saw palmetto extract is further preferablystandardized to contain at least 85% fatty acids and sterols.

The tocotrienols and tocopherols for use in the compositions of thedisclosure may be combined in a complex containing about 78%tocotrienols and about 22% tocopherols by weight.

The iodine for use in the compositions of the disclosure may be obtainedfrom kelp, e.g., Laminara digitata. In some embodiments, the iodine isisolated from kelp. In other embodiments, the iodine is provided bykelp.

The low molecular weight collagen is preferably hydrolyzed Type I andType III collagen having a molecular weight of less than about 3000daltons.

In one embodiment, the composition of the disclosure comprises fromabout 100 mg to about 1000 mg of an extract of Curcuma longa, from about100 mg to about 1000 mg of an extract of the roots and leaves ofWithania somnifera, at least about 200 mg of saw palmetto extract, andfrom about 225 mcg to 300 mcg of iodine.

In another embodiment, the composition of the disclosure comprises atleast about 200 mg of curcumin, at least about 100 mg of withanolides,at least about 500 mg of bioactive saw palmetto, preferably standardizedto contain at least about 85% fatty acids and sterols, and one or moreof the following: at least about 200 mg of saw palmetto extract, about10 mg to about 1000 mg of tocotrienol and about 50 mg to about 1000 mgof tocopherols present in a complex comprised of about 78% tocotrienolsand about 22% tocopherols, at least about 225 mcg of iodine, at leastabout 5 mg of piperine, about 500 mg to about 2000 mg of hydrolyzedTypes I and III collagen having a molecular weight of less than about3000 daltons, and/or about 100 mg to about 1000 mg of hyaluronic acid.

For female subjects an implementation of a composition of the disclosuremay contain at least about 200 mg of curcumin, at least about 100 mg ofwithanolides, and at least about 200 mg of bioactive saw palmetto,preferably standardized to contain at least about 85% fatty acids andsterols, and one or more of the following: at least about 200 mg of sawpalmetto extract, about 10 mg to about 1000 mg of tocotrienol and about50 mg to about 1000 mg of tocopherols present in a complex comprised ofabout 78% tocotrienols and about 22% tocopherols, at least about 225 mcgof iodine, at least about 5 mg of piperine, about 500 mg to about 2000mg of hydrolyzed Types I and III collagen having a molecular weight ofless than about 3000 daltons, and/or about 100 mg to about 1000 mg ofhyaluronic acid.

The compositions of the disclosure may also include one or more of thefollowing ingredients: green tea extract, L-methionine, L-cysteinehydrochloride, resveratrol, capsaicin, biotin, selenium, Vitamin D,Vitamin A, Vitamin C, choline, calcium, and/or copper.

The disclosure further provides a method of promoting hair growth andreducing hair loss in a subject experiencing hair loss of the scalp, byadministering to the subject an effective amount (e.g. an amounteffective to promote hair regrowth, slow the progression of hair loss,etc.) of said composition comprising at least about 200 mg of curcumin,at least about 100 mg of withanolides, and at least about 200 mg ofbioactive saw palmetto, preferably standardized to contain at leastabout 85% fatty acids and sterols, and one or more of the following: atleast about 200 mg of saw palmetto extract, about 10 mg to about 1000 mgof tocotrienol and about 50 mg to about 1000 mg of tocopherols presentin a complex comprised of about 78% tocotrienols and about 22%tocopherols, at least about 225 mcg of iodine, at least about 5 mg ofpiperine, about 500 mg to about 2000 mg of hydrolyzed Types I and IIIcollagen having a molecular weight of less than about 3000 daltons,and/or about 100 mg to about 1000 mg of hyaluronic acid.

The compositions and method of the disclosure for alleviating hair loss,may be effective to improve hair loss caused by, for example, forms ofalopecia including androgenetic alopecia, alopecia areata, alopeciamucinosa, telogen effluvium, chronic inflammation, extreme and/orchronic stress, diabetes, cellulitis, hair treatments, hereditarydisorders, hormonal changes, hyperthyroidism, hypothyroidism,malnutrition, lupus, medication side effects, including fromchemotherapy and birth control, radiation, aging and trichotillomania.

In an implementation, the disclosure provides methods for the treatmentand/or reduction of hair loss in a subject, comprising administering tothe subject in a pharmaceutically suitable vehicle, an effective amountof a composition of the disclosure comprising at least about 200 mg ofcurcumin, at least about 100 mg of withanolides, and at least about 200mg of bioactive saw palmetto, preferably standardized to contain atleast about 85% fatty acids and sterols, and one or more of thefollowing: at least about 200 mg of saw palmetto extract, about 10 mg toabout 1000 mg of tocotrienol and about 50 mg to about 1000 mg oftocopherols present in a complex comprised of about 78% tocotrienols andabout 22% tocopherols, at least about 225 mcg of iodine, at least about5 mg of piperine, about 500 mg to about 2000 mg of hydrolyzed Types Iand III collagen having a molecular weight of less than about 3000daltons, and/or about 100 mg to about 1000 mg of hyaluronic acid. Thecompositions can additionally include further amounts of nutrientsnecessary and beneficial hair growth which are known to those havingordinary skills in the art.

“Pharmaceutically suitable vehicle” as used herein refers to a non-toxicsolid, semisolid (also referred to as “softgel”) or liquid filler,diluent, encapsulating material or formulation auxiliary of any type,suitable for the particular route of administration and desired releaserate (e.g. immediate or controlled release) of the active compounds, andare well known in the art. Pharmaceutically suitable vehicles andexcipients that may be used to formulate oral dosage forms are describedin the Handbook of Pharmaceutical Excipients, American PharmaceuticalAssociation, Arthur H. Kibbe (2000), incorporated herein by reference inits entirety.

The bioactive compounds in the compositions of the disclosure may becombined in a single dosage form or for unit-dose or multi-doseadministration. The compositions can be formulated into suitablepreparations for administration to a subject, such as solutions,suspensions, tablets, dispersible tablets, capsules, powders, sustainedrelease, for oral administration or in sterile solutions or suspensionsfor parenteral administration, as well as transdermal patch preparation,nasal formulation and dry powder inhalers et al. The compositions mayalso be formulated as liquid dosage forms such as elixir, suspension orsyrup. The compositions are formulated into compositions usingtechniques and procedures well known in the art.

Dosage of the therapeutic agent(s) of the disclosure is dependent uponmany factors including, but not limited to, the severity of the hairloss, the subject's age, general health and individual response to thecompositions of the disclosure. Accordingly, dosages of the compositionscan vary and be readily adjusted, depending on each subject's response.

In one implementation of the disclosure, the compositions of thedisclosure may be administered to a subject in an amount of at leastapproximately 1800 mg per day as a single dose, or may be divided intotwo or more dosages administered throughout a 24 hour period. Ingestingat mealtimes may improve absorption of some of the components of thecompositions of the disclosure. The time of day the given dose orfraction of the given dose is administered can vary by day. Thecompositions of the disclosure may be taken on a daily basis untildesired hair growth is achieved, or indefinitely.

In addition to oral dosage forms, the compositions of the disclosure maybe incorporated with other ingredients into food, for example by addingthe compositions to mixtures used to prepare a “food bar,” cookie, cakeor other edible item. Mixtures of ingredients for preparing nutritionbars and other baked and non-baked items are known. Flavoring andsweetener may be added to mask any “medicine taste” of the compositionsof the disclosure. Preservatives may be added to improve shelf life.

In accordance with the practice of the disclosure, the subject may be ahuman. The subject may also be a mammal, such as a monkey, ape, dog,cat, cow, pig, horse, sheep, rabbit, mouse, rat or a bird.

The person of ordinary skill in the art will recognize that additionalingredients can be used in the compositions and methods of the presentdisclosure, for example to promote hair health and appearance, whilemaintaining effectiveness or enhancing the activity of the compositionsin promoting hair growth and reducing hair loss.

Example 1

The male subject was a 49-year old male. He began to notice mild hairthinning at the age of 28. However, the hair loss became significantlymore pronounced after he underwent radiation therapy for thyroid cancerat the age of 32. Over the next 17 years, he went to numerous physiciansand took the only FDA-approved pharmaceuticals for hair loss (minoxidiland finasteride) but the improvement was minimal and didn't stall hisprogression to Stage III Vertex/Stage IV MPHL on the Hamilton-Norwoodscale. During this time he also tried several natural supplements andtopical formulations, but did not see any noticeable improvement. Priorto taking the implementations of the disclosure described herein, he hadtaken Serenoa repens alone and biotin alone, which did not result in anoticeable cessation of hair loss or new hair growth. In 2012 he wasadditionally diagnosed with Rheumatoid Arthritis (RA), which is anautoimmune condition that creates a pro-inflammatory state in the bodyand significantly affects joints. The subject was also suffering fromchronic stress at this time. The subject notes that as a result of hiscondition his hair loss and the quality of his hair also worsened.

The subject was first given Curcumin extracted from Curcuma Longastandardized to 95% Curcuminoids including: curcumin, desmethoxycurcumin, bis-desmethoxy curcumin and volatile oils of turmeric rhizome(BCM-95®, Dolcas-Biotech, LLC, Chester, N.J.) in amounts of at least 200mg a day. To improve curcumin absorption and bioavailability, it wastaken together with 5 mg of standardized extraction of piperine. Aftercontinuing this regimen for 3 months and in addition to improvement ofhis RA symptoms, he noted decreased hair shedding and slightly improvedhair thickness and quality. During month 4, the subject was additionallygiven a daily 250 mg dose of Ashwagandha extracted from Withaniasomnifera, containing at least 8% withanolide glycosides and 32%oligosaccharides from the roots and leaves (Sensoril®, Natreon, NewBrunswick, N.J.) for stress associated with his condition and work. Henoted that month that there was a further decrease in his hair loss andsome small growth of new hairs. During month 5, the subject wasadditionally given a daily dose of Certified Organic saw palmettoextract Standardized 85-95% fatty acids (Valensa Eustis, Fla.) in theamount of 640 mg a day. During that month he experienced significant newgrowth at the frontal hairline and temples, a decrease in hair loss andimprovement in hair quality. During month 6, the subject added a 100 mgdose of tocotrienol/tocopherol complex comprising 78% tocotrienols and22% tocopherols (Tocomax™ 20%, Carotech, Malaysia) a day. This additionlead to further improvement in new hair growth at the hairline and thevertex and his hair became less brittle and smoother. Lastly, in month7, He was additionally given approximately 1000 mg of hydrolyzed marinecollagen Types I and III (Youtheory, Tustin, Calif.) and 100 mg ofhyaluronic acid (NOW Foods, Bloomingdale, Ill.). At the end of month 7the subject reported improvement in hair density, thickness, andcontinued new hair growth. The subject's progression is tabulated inFIG. 3.

Before initiation of the experiment, the subject had a bald spot on hiscrown covering an area of approximately 78 cm². Upon evaluation after 7months, the results showed that the progression of his hair loss and therecession of the frontal hairline were stalled. There was also notableand measurable new growth at the hairline, temples and vertex. Theoriginal bald spot had been reduced to an area of approximately 38 cm²,or an increase of hair growth of approximately 40 cm². Further, therewas increase in the thickness and overall quality of hair.

After having significant loss of scalp hair for a period of 17 years,the subject experienced significant new hair growth and overall increasein thickness of scalp hair. The subject experienced no noticeable sideeffects from consumption of the composition.

Example 2

The subject, a 36 year-old male with early stages of MPHL (stage II onthe Hamilton-Norwood scale), began taking an implementation of thedisclosure consisting of 200 mg curcumin, 5 mg of piperine, 250 mg ofwithanolides, 640 mg of Serenoa repens, 100 mg Tocotrienol/Tocopherolcomplex comprising 78% tocotrienols and 22% tocopherols, 900 mg ofHydrolyzed Collagen Types I and III, 100 mg Hyaluronic Acid, 5 mgVitamin A, 3 mg Vitamin D, 60 mg Vitamin C, 0.2 mg Selenium, 3 mgBiotin, 5 mg Capsaicin, 50 mg Resveratrol, 100 mg L-Methionine and 100mg L-Cysteine Hydrochloride. After 6 months of daily ingestion thecomposition, he not only noticed a halt to the progression of hisalopecia, but he also noted new hair growth, especially in thefront—filling in his receding hairline. His hair also became thicker andmore manageable. His wife and colleagues noted the increased hair growthand thickness. He even decided to start growing his hair longer.Overall, he also noted that he was feeling overall much healthier andeven experienced increased libido.

Example 3

The subject was a 51 year-old female with moderate to severe stage 2(Ludwig scale) manifesting in typical female pattern hairloss—significant widening of the part, diffuse hair loss and thinning ofthe crown. She started noticing hair thinning and loss in her 20's andtried many different products, without improvement. She concurrentlysuffered from chronic stress. The subject began taking began taking animplementation of the disclosure consisting of 200 mg curcumin, 5 mg ofpiperine, 250 mg of withanolides, 200 mg of Serenoa repens, 100 mgTocotrienol/Tocopherol complex comprising 78% tocotrienols and 22%tocopherols, 900 mg of Hydrolyzed Collagen Types I and III, 100 mgHyaluronic Acid, 5 mg Vitamin A, 3 mg Vitamin D, 60 mg Vitamin C, 0.2 mgSelenium, 3 mg Biotin, 5 mg Capsaicin, 50 mg Resveratrol, 100 mgL-Methionine and 100 mg L-Cysteine Hydrochloride daily. After a 6 monthperiod, she saw dramatic improvement not only in quality and shine, butalso saw significant hair growth within 7 months of use.

Example 4—Genemarkers™ Cytotoxicity & Cell Proliferation Analysis ofHuman Dermal Papillae Cells Treated with Test Materials for 24 or 48Hours

This study was conducted to determine the effect of test materials oncell proliferation of human follicular dermal papillae cells (DPCs). Twodifferent types of assays were used to measure proliferation, MTT assay& BrdU ELISA.

Example 4.1—MTT Assay

The MTT cell proliferation assay measures cell proliferation rate andconversely when metabolic events lead to apoptosis, the reduction incell viability. Cell viability is measured via the reduction oftetrazolium salts. The yellow tetrazolium MTT (3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) is reduced bymetabolically active cells, in part by the action of dehydrogenaseenzymes. The resulting intracellular purple formazan substance can besolubilized and quantified by spectrophotometry. MTT assays performedconfirmed the viability and proliferation ability of DPCs in thepresence of combinations of Ashwaghanda, Saw Palmetto, and Kelp.

Example 4.2—BrdU ELISA

Halogenated nucleotides such as pyrimidine analog5-bromo-2′-deoxyuridine (BrdU) are incorporated into cellular DNA duringcell proliferation using an anti-BrdU antibody. When cells are culturedwith labeling medium that contains BrdU, the pyrimidine analog isincorporated in place of thymidine in newly synthesized DNA ofproliferating cells. A BrdU mouse antibody is then added to detect theincorporated BrdU. Anti-mouse IgG is added and used to recognize thebound detection antibody. A substrate TMB is added to develop color andthe magnitude of the absorbance for the developed color is proportionalto the quantity of BrdU incorporated into the cells, which is a directindication of cell proliferation (Leif, R. C. et al. (2004) Cytometry A58, 45-52).

The BrdU Proliferation Assay was performed after 72 hours of treatmentwith test materials in the following groups: Ashwaghanda alone, Kelpalone, Saw Palmetto alone, and combinations of Kelp and Saw Palmetto,Ashwaghanda and Kelp, Ashwaghanda and Saw Palmetto, and Kelp,Ashwaghanda and Saw Palmetto, solubilized respectively in 0.8% DMSO. Theresults are shown in FIG. 4.

Positive controls, containing 20% serum, both showed higherproliferation vs the other control groups containing 1% serum. Thenegative control, labeled “Background”, was not given BrdU toincorporate into the DNA of dividing cells. This Background group showeda very low signal, as expected.

Increased proliferation was also seen when Kelp was added to SawPalmetto (127%) as compared to Saw Palmetto alone (94%). The resultsindicate an increase in cell proliferation when adding Kelp toAshwaghanda (108%), compared to Ashwaghanda alone (51%). Notably, theaddition of Kelp to the combination of Ashwaghanda and Saw Palmettoprovided 171% increase in cell proliferation as compared to the 104%increase with Ashwaghanda and Saw Palmetto alone. The addition of kelpto the above synergistic ingredient combinations shows increasedproliferation of follicular dermal papillae cells.

Example 5—Safety and Efficacy in Promoting Hair Growth in Women withSelf-Perceived Thinning Hair

The objective of this study was to evaluate the safety and efficacy ofdaily supplementation with an embodiment of the disclosure comprised ofat least 200 mg of curcumin, at least 100 mg of withanolides, and atleast 200 mg of bioactive saw palmetto, standardized to contain at least85% fatty acids and sterols, 10 mg to 1000 mg of tocotrienol and 50 mgto 1000 mg of tocopherols present in a complex comprised of 78%tocotrienols and 22% tocopherols, 225 mcg of iodine, 5 mg of piperine,500 mg to 2000 mg of hydrolyzed Types I and III collagen having amolecular weight of less than 3000 daltons, and 100 mg to 1000 mg ofhyaluronic acid to promote hair growth in women with self-perceivedthinning hair.

Methods:

Forty healthy women 21-65 years old with Fitzpatrick skin types I-IV andself-perceived thinning hair were enrolled and randomized indouble-blind fashion to receive a composition of the present disclosure(n=26) or placebo (n=14) once daily. The subjects were evaluated atbaseline, 3 months and 6 months. A 2 cm² area of the scalp was selectedand marked via triangulation along the juncture of the frontal andlateral hairline. The primary endpoints evaluated were a change in thenumber of vellus and terminal hairs on phototrichogram analysis at Day90 and Day 180. Secondary endpoints included blinded investigatorphysician global hair assessments on hair growth and quality,improvement in terminal hair diameter, hair mass index measurements, andsubjects also completed Self-Assessment, Ease of Use and Quality of Lifequestionnaires at each visit.

Results:

As shown in FIG. 5A, there was a significant increase in the number ofterminal hairs in the target area at both Day 90 (3 months) and Day 180(6 months) over baseline in the active group vs placebo (p<0.0001). At 6months, this translated into a 10.3% improvement in terminal hair growthfor the active group vs only 3.5% for placebo.

As shown in FIG. 5B, there was a significant increase in the number ofvellus hairs in the target area at both Day 90 (3 months) and Day 180 (6months) over baseline in the active group vs. placebo (p<0.0001). At 6months, this translated into a 16.2% improvement in vellus hair growthfor the active group vs. a decrease of 2.3% for placebo.

As shown in FIG. 5C, the active group had statistically significantimprovement versus placebo in hair growth at 6 months. The mean hairgrowth global improvement scale scores were 1.08 (1.1) for the activegroup and 0.08 (0.76) for the placebo group (p<0.016).

As shown in FIG. 5D, there was significant improvement in the activegroup compared to the placebo group at both 3 and 6 months. At 6 monthsthe mean hair quality global improvement scale scores were 1.12 (0.87)for the active group and 0.08 (0.76) for the placebo group (p<0,05).Hair quality was rated based on hair brittleness, dryness, texture,shine, scalp coverage and overall appearance.

Images from an active subject at baseline, 3 months and 6 months areshown in FIG. 6A-FIG. 6F.

Table 1 shows the results of a self-assessment questionnaire aftertaking active composition for 6 months.

TABLE 1 % OF SUBJECTS IMPROVED QUALITY 80.8%* Overall hair growth 73.1%*Overall hair volume 80.8%* Thickness of hair body 23.1%* Hair color76.9%* Amount of noticeable new hair 73.1%* Hair growth rate 15.4%*Stress level 15.4%* Anxiety level 19.2%* Overall well-being 23.1%* Skinsmoothness 26.9%* Overall skin health

Safety Assessment:

There were no reported adverse events or side effects. Subjects found itto be well tolerated and easily incorporated into their daily routines.

Conclusion:

The results of this study indicate that daily supplementation with theactive composition of the disclosure resulted in increased hair growthin women with self-perceived thinning hair. A vast majority of treatedsubjects also reported positive results in key hair quality and wellnessattributes. The study composition provides a safe and effectivetherapeutic option for improving hair growth in women with thinninghair.

ADVANTAGES OF THE INVENTION

The compositions of the disclosure thus produced significant and visiblebenefits in mitigating hair loss and promoted new hair growth.

While the present disclosure has been described in terms of exemplaryaspects, those skilled in the art will recognize that the presentdisclosure can be practiced with modifications in the spirit and scopeof the appended claims. These examples and embodiments given above aremerely illustrative and are not meant to be an exhaustive list of allpossible designs, aspects, applications or modifications of the presentdisclosure.

What is claimed is:
 1. A method of improving hair loss caused byandrogenetic alopecia, alopecia areata, alopecia mucinosa, telogeneffluvium, chronic inflammation, extreme and/or chronic stress,diabetes, cellulitis, hair treatments, hereditary disorders, hormonalchanges, hyperthyroidism, hypothyroidism, malnutrition, lupus,medication side effects, radiation, aging and trichotillomania,comprising administering to a subject in need thereof an effectiveamount of a composition comprising: about 100 mg to 1000 mg of anextract of Curcuma longa, from about 100 mg to 1000 mg of an extract ofthe roots and leaves of Withania somnifera, at least about 200 mg of sawpalmetto extract, from about 225 mcg to 300 mcg of iodine, and apharmaceutically acceptable encapsulating material, for a timesufficient to improve hair loss.
 2. The method of claim 1, wherein saidiodine is provided by kelp.
 3. The method of claim 1, wherein thecomposition further comprises from about 100 mg to about 1000 mg oftocotrienols and tocopherols.
 4. The method of claim 1, wherein thecomposition further comprises low molecular weight collagen andhyaluronic acid.
 5. The method of claim 4, wherein said collagen is TypeI and Type III collagen and has a molecular weight of less than 5000daltons.
 6. The method of claim 4, wherein said collagen is present inan amount from about 500 mg to about 2000 mg, and said hyaluronic acidis present in an amount from about 100 mg to about 1000 mg.
 7. Themethod of claim 1, wherein the composition further comprises at leastabout 5 mg of piperine.
 8. The method of claim 1, wherein thecomposition further comprises one or more compounds selected from thegroup consisting of green tea extract, L-methionine, L-cysteinehydrochloride, resveratrol, capsaicin, biotin, selenium, Vitamin D,Vitamin A, Vitamin C, choline, calcium or copper.
 9. A method ofimproving hair loss caused by androgenetic alopecia, alopecia areata,alopecia mucinosa, telogen effluvium, chronic inflammation, extremeand/or chronic stress, diabetes, cellulitis, hair treatments, hereditarydisorders, hormonal changes, hyperthyroidism, hypothyroidism,malnutrition, lupus, medication side effects, radiation, aging andtrichotillomania, comprising administering to a subject in need thereofan effective amount of a composition comprising: at least about 200 mgof curcumin, at least about 100 mg of withanolides, at least about 200mg of saw palmetto extract, at least about 100 mg of tocotrienols andtocopherols comprising a complex of about 78% tocotrienols and about 22%tocopherols, at least about 225 mcg of iodine, at least about 1000 mg ofType I and III collagen having a molecular weight of less than about3000 Daltons, at least about 100 mg of hyaluronic acid, and apharmaceutically acceptable encapsulating material, for a timesufficient to improve hair loss.
 10. A method of improving hair losscaused by medication side effects, comprising administering to a subjectin need thereof an effective amount of a composition comprising: about100 mg to 1000 mg of an extract of Curcuma longa, from about 100 mg to1000 mg of an extract of the roots and leaves of Withania somnifera, atleast about 200 mg of saw palmetto extract, from about 225 mcg to 300mcg of iodine, and a pharmaceutically acceptable encapsulating material,for a time sufficient to improve hair loss.
 11. The method of claim 10,wherein the medication side effects are caused by chemotherapy.
 12. Themethod of claim 10, wherein said iodine is provided by kelp.
 13. Themethod of claim 10, wherein the composition further comprises from about100 mg to about 1000 mg of tocotrienols and tocopherols.
 14. The methodof claim 10, wherein the composition further comprises low molecularweight collagen and hyaluronic acid.
 15. The method of claim 14, whereinsaid collagen is Type I and Type III collagen and has a molecular weightof less than 5000 daltons.
 16. The method of claim 14, wherein saidcollagen is present in an amount from about 500 mg to about 2000 mg, andsaid hyaluronic acid is present in an amount from about 100 mg to about1000 mg.
 17. The method of claim 10, wherein the composition furthercomprises at least about 5 mg of piperine.
 18. The method of claim 10,wherein the composition further comprises one or more compounds selectedfrom the group consisting of green tea extract, L-methionine, L-cysteinehydrochloride, resveratrol, capsaicin, biotin, selenium, Vitamin D,Vitamin A, Vitamin C, choline, calcium or copper.
 19. A method ofimproving hair loss caused by medication side effects, comprisingadministering to a subject in need thereof an effective amount of acomposition comprising: at least about 200 mg of curcumin, at leastabout 100 mg of withanolides, at least about 200 mg of saw palmettoextract, at least about 100 mg of tocotrienols and tocopherolscomprising a complex of about 78% tocotrienols and about 22%tocopherols, at least about 225 mcg of iodine, at least about 1000 mg ofType I and III collagen having a molecular weight of less than about3000 Daltons, at least about 100 mg of hyaluronic acid, and apharmaceutically acceptable encapsulating material, for a timesufficient to improve hair loss.